This project is directed to the separation, characterization, definition of function(s) and mechanisms(s) of action of macrophages (M phi), thymus-derived cells, T cells, and precursors of antibody producing cells, B cells, in the generation and regulation of antibody responses in tissue culture systems. Methodology has been developed for separating and characterizing M phi, T cells and B cells. The critical function of antigen presentation by M phi to responding T and B cells will be analyzed with attention to M phi-membrane components involved. The mechanisms of genetic restrictions governing efficient M phi-immune T cell interactions in the development of secondary antibody responses will be analyzed and the implications of these restrictions for the nature of the T cell receptor for antigen will be probed. The cellular site and mechanism of action of antisera against defined membrane components of T and B cells which suppress antibody responses will be analyzed to probe mechanisms of interactions among T and B cells which result in the switch from IgM to IgG antibody production. These investigations will further the understanding of fundamental mechanisms in the generation and regulation of expression of immune responses. This understanding should lead to a better appreciation of mechanisms of disease processes with immunological components, such as autoimmune diseases, and, to development of appropriate immunization protocols for protection against infectious and allergic diseases.